Immunology: Bowel disease and bone loss

Immunity 19, 849–861 (2003)

Certain types of bone disorder and inflammatory bowel disease probably occur when the body mounts an immune response against itself. A subset of immune cells, known as CD4-expressing T cells, is overactive in these circumstances — but their exact role in disease is unclear.

When mice are engineered to lack a key regulator of these T cells, the cells become hyperactive and the mice develop colon inflammation and osteoporosis-like bone wasting. A. J. Ashcroft et al. now report that the animals' condition is caused by a protein called RANKL. They find that the hyperactive T cells produce too much of the protein, which then contributes to bone breakdown and bowel inflammation. When the mice are treated with osteoprotegerin — a protein that interferes with RANKL's binding to its receptor — bone loss is reversed and colon inflammation lessens. The study suggests that some bone diseases and intestinal problems may have a common cause.

Helen R. Pilcher

Networks: Special friends

Phys. Rev. Lett. 91, 247901 (2003)

Internet connections: the world's e-mail network. Credit: CAIDA

In epidemiology, topology matters: the structure of a network in which an infectious disease spreads can have a big influence on how easy it is to arrest the disease. Some social networks seem to be 'scale-free'— bound together by just a few very highly connected individuals (hubs). An ideal immunization strategy for, say, preventing epidemics of sexually transmitted disease in such a network would be to find and immunize these hubs. But that can be extremely hard to do. Random immunization, on the other hand, is relatively ineffective, for there is only a low chance of eliminating hubs short of immunizing almost everyone, which is costly. The same principles hold true for containing computer viruses, as electronic networks seem also to be scale-free.

Reuven Cohen and colleagues now propose an alternative strategy. On the basis of mathematical modelling, they suggest that immunizing just a small fraction of the acquaintances, chosen at random, of randomly selected individuals will dramatically reduce the epidemic threshold — the fraction of all individuals in the network that must be immunized to prevent an epidemic. Although this strategy might sound little different from random immunization, it exploits the fact that acquaintances tend on average to have more connections than individuals selected at random: the mere fact of being a 'friend' makes them special.

Philip Ball

Evolutionary biology: Sexual conflict costs

Proc. R. Soc. Lond. B doi:10.1098/rspb.2003.2588

For a female dung fly, having a choice of mates comes at a price. Females selected for the rough-and-tumble of multiple mating do worse than monogamous strains when they then mate only once, say Oliver Y. Martin and his colleagues.

The researchers subjected dung flies, Scathophaga stercoraria, to ten generations of artificial selection. One set of females was allowed multiple matings (polyandry), while monogamy was forced on another set. Martin et al. then looked at the fitness of each line when mated just once: they found that polyandrous females had shorter lives, and fewer eggs and offspring.

When females mate with many males, as happens in most insects, the conflict between the sexes increases. Females wish to control whose sperm they use to fertilize their eggs, but evolution will drive males to try and manipulate females into using their sperm. Removing this competition reveals the costs that adapting to fight the battle imposes on females. It is not known what reduces the fitness of polyandrous females, although it has shown that their immune systems are weaker than those of their monogamous counterparts.

John Whitfield

Chemical detection: Odour eater

Chem. Commun. 2970–2971 (2003)

As Agatha Christie well knew, the smell of bitter almonds can indicate cyanide in the air and death not far away. In reality, industrial workers who might be exposed to this toxic gas need appropriate respiratory protection. Michael J. Hudson et al. describe a new material that could be used in such apparatus as a filter for hydrogen cyanide gas, and which has many practical benefits compared with conventional activated-carbon systems.

The material is an ordered mesoporous silica that has been doped with sodium peroxydisulphate. It is simple to synthesize and can filter out hydrogen cyanide for longer than can a range of other porous materials. The doped silica also functions in an aqueous environment, whereas existing filter materials tend to fail at high humidity. In addition, it does not contain the carcinogenic chromate ions that are present in some conventional materials; nor does it produce cyanogen, another poisonous molecule.

Hudson et al. admit that further development is needed, in particular to improve the stability of the material. But its efficacy as a cyanide filter could well have fooled Miss Marple.

Rosamund Daw

Cancer: Creating instability

J. Cell Biol. 163, 949–961 (2003)

Colorectal cancer is one of the most common cancers worldwide. Although the cause remains unclear, tumour progression may result from the abnormal gain or loss of chromosomes during cell division — a process called chromosome instability. Rebecca A. Green and Kenneth B. Kaplan propose that this instability is due to chromosomes coming unglued from the molecular tethers that are responsible for ordering their movements.

Green and Kaplan noticed that colorectal tumour cells, known to have high rates of chromosome instability, also showed a loss of microtubules in the spindle apparatus. This is the delicate intracellular network of fibres that coordinate the distribution of chromosomes during cell division. A more detailed look revealed that much of the microtubule loss occurred at the sites where the fibres attach to each chromosome. As a result, the chromosomes did not line up or move appropriately as the cells divided.

Coincidently, these attachment sites also contain the adenomatous polyposis coli (APC) protein, the gene for which is frequently mutated in human colorectal cancer. When the researchers introduced a mutated form of APC into healthy cells, they saw a similar disruption of the spindle and abnormal chromosome movements to that observed in tumour cells. Thus, a similar mutation in healthy intestinal cells could predispose the cells to further genetic abnormalities and eventually lead to tumour formation.

Brian Fiske